Our previous studies on pre- and neo-natal (early) exposure of animals to ethanol have suggested that the administration of relatively low levels of ethanol resulted in long-term behavioral changes in mice. Our investigations and those of others indicate that changes in neurotransmitter systems may mediate the behavioral changes. Other studies suggest the early or chronic administration of drugs may induce long-term changes in tolerance or the ability to develop tolerance and physical dependence. We plan to use different genetic strains of mice to establish an animal model for the long-term effects of early barbiturate consumption on the central nervous system and behavior. We will study in adulthood the changes in tolerance, and the ability to develop tolerance and physical dependence following early barbiturate administration; changes from normal patterns in the susceptibility to audiogenic seizures, male agonistic behavior and predatory behavior will be investigated in adult offspring. The sensitive periods to the barbiturate-induced behavioral changes will be identified. Depending on the behavioral changes that will be found, we will use biochemical techniques to study the changes in the metabolism and function of the neurotransmitters involved. Thus, the cholinergic, cateolaminergic and adrenergic systems may be studied. The biochemical and the behavioral changes will be correlated across strains and with the sensitive periods. Such studies may put the behavioral and biochemical events in a causal relationship and provide insight into the mechanism of barbiturate action on the developing CNS as well as some of the normal determinants of behavior. Such studies may also provide background for research on prevention of the effect of early barbiturate administration.